Having won the 2000 NRL Premiership, the Broncos traveled to England to play against 2000's Super League V champions, St Helens R.F.C., for the 2001 World Club Challenge, with Lockyer playing at fullback in Brisbane's loss. In March 2001, Lockyer was approached by the Australian Football League club Essendon regarding an unprecedented switch of codes, and was offered a contract subsequent to a successful trial. However Lockyer chose to stay committed to rugby league. Later in 2001, following Queensland captain Gorden Tallis' season-ending neck injury before the second game of the 2001 State of Origin series, the Maroons' captaincy was handed to Lockyer. In the third and deciding game of the series, Lockyer was named man-of-the-match, having scored two tries and kicked four goals to help Queensland to victory. Lockyer's heroic game 3 performance, however, has been overshadowed by the return to State of Origin from Queensland legend Langer after an SOS from coach Bennett. Despite the lack of media coverage, Lockyer was still awarded the Ron McAuliffe Medal as Queensland player of the series. Brisbane started off the 2001 season in the same form they ended 2000, and sat 2nd on the ladder after 19 rounds. But a late season collapse, losing 6 straight to limp into the finals in 5th position. Lockyer was one of Brisbane's best, even during the losing streak, but couldn't prevent a 22-6 loss to Cronulla in the Qualifying Final. They bounced back against the St George Illawarra Dragons to the tune of 44-28, a game which set the record for highest scoring match in NRL Finals history, before their season came to an end with a 24-16 loss to the minor premiers Parramatta. Lockyer walked away with a bevy of awards for his performances, including Dally M Fullback Of The Year and Dally M Representative Player Of The Year. At the end of the season, Lockyer went on the 2001 Kangaroo tour of Great Britain. He played at fullback in all three Ashes tests, scoring tries in the last two.
In Round 8, Lockyer played his 300th first grade game, although the occasion was soured by a 28-12 loss to Newcastle during which a section of EnergyAustralia Stadium was left without power at half time. Returning to the Queensland side after a 1 year absence, Lockyer resumed his role as captain and led the Maroons to a record 4th consecutive series victory. Lockyer sustained a knee injury in the dead-rubber Game 3, which sidelined him for 3 weeks. In that time, Brisbane had fallen to 10th on the ladder, but after a then-club record 56-0 drubbing against Canberra in his first game back, Brisbane won 5 straight matches to finish 6th in Ivan Henjak's first year as head coach- and Brisbane's first season coached by someone other than Wayne Bennett, after the supercoach left for the Dragons. Brisbane beat the Titans 40-32 in the Qualifying Final, tying the record for highest scoring final that they had set in 2001, and set up a semi final showdown with Bennet's Dragons at Suncorp Stadium. Brisbane dominated the minor premiers and advanced to the Preliminary Final with a 24-10 win, but the result was soured by a fractured ankle suffered by Lockyer's halves partner Peter Wallace. The only other halfback on Brisbane's roster was Ben Hunt, who at the time had played just 2 first grade games. They named rookie utility Alex Glenn at halfback, only to move veteran back rower Tonie Carroll into the halves at the last minute. Ultimately, they were probably doomed no matter what they did, as Melbourne ended their season for the third year in a row with a 40-10 rout. During the 2009 Four Nations tournament, in which Lockyer captained Australia to victory, he also broke records for most-capped Australian player and most games for Australia as captain.