T'Challa is heir to the centuries-old ruling dynasty of the African kingdom Wakanda, and ritual leader of its Panther Clan. His mother died in childbirth, earning him the enduring hatred of his adopted elder brother, Hunter, who also resented T'Challa for supplanting him in the royal household. Hunter would become the White Wolf, leader of the Hatut Zeraze (Dogs of War), the Wakandan secret police. Their father T'Chaka remarried, but his second wife, Ramonda, seemingly ran away with another man when T'Challa was eight. When T'Challa was a teenager, T'Chaka was murdered by Klaw, a Dutchman seeking to plunder the rare Vibranium metal unique to Wakanda, but T'Challa used Klaw's own weapon to maim him and drive him off. T'Challa studied in Europe and America, then underwent ritual trials in Wakanda - including defeating his uncle S'yan, the existing Black Panther - to win the heart-shaped herb, enhancing his abilities and linking him spiritually to the Panther God Bast. Now Wakanda's ruler as the Black Panther, he disbanded and exiled the Hatut Zeraze and continued transforming his country into a high-tech wonderland. When tribal war broke out, T'Challa restored peace by condemning the Jabari tribe, and by picking Dora Milaje ("Adored Ones") from rival tribes to serve as his personal guard and ceremonial wives-in-training.

Taught by his father to think two steps ahead of enemies and three steps ahead of friends, T'Challa saw the world's super-beings as potential threats to Wakanda. Inviting the Fantastic Four to visit him, he forced them into a series of tests, then allied with them against a returning Klaw. He also joined the American-based Avengers to spy on them from within, but soon came to regard them as true friends and staunch allies. He adopted the identity of teacher Luke Charles while in America, romancing singer Monica Lynne, later his fiancée. Dividing his time between Wakanda and America for years, he battled foes such as Jabari malcontent M'Baku the Man-Ape, rebel leader Erik Killmonger, the snake-charmer Venomm (later an ally), voodoo charlatan Baron Macabre, the Ku Klux Klan, the ghostly Soul-Strangler, the soaring Wind Eagle, mutated drug czar Solomon Prey, arms dealer Moses Magnum and the Supremacists of Azania. He also fought Kiber the Cruel during a quest for the mystic time-shifting artifacts known as King Solomon's Frogs; these produced an alternate version of T'Challa from a future ten years hence, a merry telepathic Panther with a terminal brain aneurysm. Placing his dying future self in cryogenic storage, T'Challa broke off his engagement with Monica since he feared he had no future to give her. Wakanda and Atlantis subsequently came to the brink of war during the Kiber Island incident, which revealed Wakanda to be a nuclear power. Discovering his stepmother Ramonda had not run away, but instead had been kidnapped by Anton Pretorius, he rescued her from years of captivity in South Africa. T'Challa joined the Knights of Pendragon against their enemies, the Bane, learning in the process that he housed one of the Pendragon spirits himself. He was also used as a pawn in the efforts of the munitions company Cardinal Technology to escalate the civil war in the northern nation Mohannda, but exposed Cardinal with the aid of the mercenary Black Axe and the anti-war activist Afrikaa.

T'Challa's restrictions on exports of both Vibranium and Wakandan technology had long annoyed foreign powers. Xcon, an alliance of rogue intelligence agents and the Russian mafia, backed a coup in Wakanda led by Reverend Achebe. Learning Achebe was empowered by the demon Mephisto, T'Challa sold his soul in exchange for Mephisto's, abandoning Achebe and leaving Wakanda in peace; however, T'Challa's unity with the Panther God and its link to the spirits of past Panther Clan leaders forced Mephisto to forfeit the Panther's soul. T'Challa then presented the U.N. with evidence of the Xcon plot and its U.S. links, demanding sanctions against America. When Hunter and the Hatut Zeraze resurfaced during the Xcon incident, a wary T'Challa imprisoned them just prior to regaining his throne.

After T'Challa discharged Nakia from the Dora Milaje for trying to kill Monica Lynne in a fit of jealousy, Nakia was tortured by Achebe and rehabilitated by Killmonger, who shaped her into the mad warrior Malice. She was replaced in the Dora Milaje by Queen Divine Justice, an American-raised Jabari. T'Challa himself returned to the U.S. on a diplomatic mission, leaving his Washington envoy Everett K. Ross in charge as regent of Wakanda, until Killmonger tried to destroy Wakanda's economy; to thwart this, the Panther nationalized all foreign companies in Wakanda, causing a global run on the stock market, which Tony Stark (Iron Man) used to secure a controlling interest in the Wakandan Design Group. Returning home, the Panther fought Killmonger in ritual combat, but was distracted at a critical juncture by Ross and beaten nearly to death. Killmonger only relented when Ross, still regent, yielded on T'Challa's behalf, unwittingly giving the Black Panther title to Killmonger. T'Challa's life was mystically saved by his allies Brother Voodoo and Moon Knight. While T'Challa recovered, Killmonger tried to join the Avengers as the new Black Panther, and Achebe enlisted super-mercenaries such as Deadpool to attack Wakanda again. During the resultant Avengers visit to Wakanda, Ross freed Hunter, whose scheming resulted in Killmonger's seeming demise and the restoration of T'Challa's title.

Wakanda next came into conflict with Deviant Lemuria during a dispute over custody of a Deviant child found in Wakanda. As tensions mounted, warships from Wakanda, the U.S. and Atlantis all entered the area, and Hunter made matters worse when he decided to force T'Challa to "reclaim his dignity" by reviving Klaw, who tried to spark outright war between the nations involved. In the end, Ross's negotiation skills and information supplied by Magneto and Doctor Doom resolved the conflict. While T'Challa faced attacks by Malice, Divine Justice was kidnapped by the Man-Ape, who learned she was the rightful Queen of his tribe. T'Challa defeated M'Baku again, though not before he uncovered the frozen future Panther. Back in New York, the criminal Nightshade resurrected the fabled Chinese monster Chiantang the Black Dragon to use against T'Challa. Black Dragon had the Panther attacked by a mind-controlled Iron Fist, whose assault caused the brain aneurysm the future Panther had foreshadowed. Nightshade, meanwhile, managed to revive the future Panther.

At the same time, T'Challa learned that White Wol] had taken over Xcon and slain most of its leaders, who had used King Solomon's Frogs to replace the U.S. President and Canadian Prime Minister with brainwashed future counterparts, allowing Xcon to secretly take over both countries. Hunter continued their plan and sought revenge on Tony Stark for his buy-out of Wakandan Design Group. Uncertain of how far along Hunter's plan was, T'Challa drew Stark out with a covert message, using financial finagling to seize control of Stark Enterprises and simultaneously annex a small Canadian island in Lake Superior, prompting the U.S. and Canadian leaders to meet to discuss this crisis. The Panther and his allies, including the future Panther, then invaded the White House and foiled Xcon's plot, un-brainwashing the duplicate leaders and returning them to their own times.

Panther and his allies returned to Wakanda, where the future Panther fell into a coma. Hoping to free her tribe, Divine Justice freed the Man-Ape, but he broke his promises of non-violence by slaying the helpless future T'Challa. The original T'Challa, by now unstable and hallucinating, attacked the Jabari tribe with the intent of wiping them out; but after nearly slaying Divine Justice, he came to his senses and stopped the battle. Unable to face what he had done, the Panther handed power to his council and hid in New York. There he mentored policeman Kasper Cole (who had adopted an abandoned Panther costume), an experience which gave T'Challa the strength to face his illness, his nation and the world. His rule has since been challenged by a revived Killmonger, an issue which remains unresolved. At the same time, T'Challa renewed his ties with the Avengers, helping them battle Scorpio, secure special United Nations status and unmask U.S. Defense Secretary Dell Rusk as the evil Red Skull; however, the team disbanded after a series of devastating assaults by an insane Scarlet Witch.