Blanchard entered World Championship Wrestling (WCW) in early 1984. Blanchard immediately entered into a feud with Mark Youngblood over the WCW Television Championship. Blanchard won the title on March 28, 1984 and defended the title against some of the top contenders in the promotion such as Ricky Steamboat, whom he faced at Starrcade '84.
After Steamboat departed WCW, Blanchard and Dusty Rhodes began a feud for the TV title. On March 16, 1985, Rhodes defeated Blanchard to win the WCW Television Championship, ending Blanchard's 353-day reign. The two continued to feud throughout the first half of 1985 with Blanchard regaining the title and losing it back to Rhodes in early July 1985 at the Great American Bash inside a steel cage; Rhodes also won the services of Baby Doll for 30 days.
After Blanchard's feud with Rhodes ended, he soon found himself immersed in another high-profile feud over the WCW United States Heavyweight Championship held by Magnum T.A.. Much like his feud with Dusty Rhodes, Blanchard's rivalry with Magnum escalated into a series of bloody and brutal matches, and became one of the top feuds in WCW. On July 21, 1985 Blanchard defeated Magnum for the U.S. Championship by punching him with a foreign object in his hand given to him by Baby Doll, who came to ringside dressed as a security guard. The feud culminated at Starrcade '85 during a brutal and extremely bloody "I quit" match held inside of a steel cage for the title. The match ended with Magnum driving a piece of a broken wooden chair into Blanchard's forehead, which was already deeply cut and bleeding profusely, forcing him to submit.
In late 1985, Blanchard fired Baby Doll as his manager, slapping her during an interview segment and ignited a feud with Dusty Rhodes, who came to her aid. James J. Dillon then became Blanchard's manager.
Throughout the latter half of 1985, Blanchard and a number of high-profile wrestlers in the company had often competed together, usually in variations of tag team matches or interfering in one another's matches if they appeared to be losing. These wrestlers included Ole Anderson, rising star Arn Anderson and Ric Flair, the biggest star in the promotion and WCW World Heavyweight Champion. In early 1986, the foursome became a solidified group and called themselves the Four Horsemen. The group quickly established dominance within the promotion by capturing numerous championships with Arn being the WCW World Television Champion and Flair as the WCW World Champion. The Horsemen feuded with the top baby faces of WCW including Magnum T.A., Nikita Koloff, Dusty Rhodes, Wahoo McDaniel, The Rock 'n' Roll Express, and The Road Warriors.
The Horsemen continued to feud with the other top stars of WCW throughout 1986 and 1987, particularly after forcing out Ole Anderson and replacing him with Lex Luger. By mid-1987, Blanchard and Anderson began competing regularly on the tag team circuit and quickly entered into a feud with the Rock 'n' Roll Express over the WCW World Tag Team Championship. The feud culminated in late September after Blanchard and Anderson won the titles after a number of high-profile matches.
Toward the end of 1987, Lex Luger defected from the Horsemen and feuded with all of them over the course of the next several months. Luger quickly formed a partnership with Barry Windham and competed in the tag team division as well. The new duo defeated Anderson and Blanchard on March 27, 1988 though they would lose the titles back to them a little more than a month later after Windham turned on Luger and became the newest Horseman.
Blanchard and Arn Anderson left WCW for the World Wrestling Federation (WWF) on September 10, 1988, losing in an 11th-hour title change to the Midnight Express tandem of Bobby Eaton and Stan Lane after a brief feud. In the WWF, Blanchard and Anderson were dubbed The Brain Busters and paired with heel manager Bobby Heenan. The team defeated Demolition for the WWF Tag Team Championship on July 18, 1989 (aired July 29 on Saturday Night's Main Event XXII), ending Demolition's historic first reign, but lost the titles back to Demolition on October 2, 1989 (aired November 4 on WWF Superstars of Wrestling).
Blanchard and Anderson were planning a return to WCW. As a result, the WWF pushed a break up angle between Heenan and the Brain Busters on the November 25, 1989 Saturday Night's Main Event XXIV (taped October 31, 1989). Bobby Heenan replaced Blanchard as part of the Heenan Family team at Survivor Series five days later.
Blanchard debuted in the American Wrestling Association (AWA) in March 1990, aligning himself with The Destruction Crew. At SuperClash IV on April 8, 1990, he defeated Tommy Jammer. He made his final appearance with the AWA in May 1990.
In 1993, World Championship Wrestling offered Blanchard a contract to reform The Four Horsemen at Slamboree 1993. Blanchard did not accept the offer, and WCW replaced him with Paul Roma. One year later, at Slamboree 1994, Blanchard appeared with WCW for a single night, wrestling Terry Funk to a double disqualification.
In January 1995, Blanchard debuted in Extreme Championship Wrestling, wrestling ECW World Heavyweight Champion Shane Douglas to a time limit draw. He challenged Douglas again in February and March, losing on both occasions.
On the March 31, 2008 edition of WWE Raw, Blanchard reunited with Arn Anderson, J.J. Dillon, and Barry Windham to salute the recently retired Ric Flair. On March 31, 2012, Tully Blanchard was inducted into the WWE Hall of Fame as a member of the Four Horsemen.