The Lancashire star, playing a first-class match for the first time since undergoing an ankle operation in January, hammered his quick-fire 83 at New Road against Worcestshire after suffering a first innings duck.
Australian team-mate Stuart Law matched his score as Lancashire reached 377 in their second innings, setting Worcestershire 268 to win.
And at stumps on day three, the hosts were 58-2 with Graeme Hick on 36.
Flintoff struck 10 boundaries and four sixes.
England Test contender Ian Bell hit a double century as Warwickshire took command of their clash with Middlesex.
Bell reached 231 on the third day as the defending champions amassed a first-innings 430 in reply to Middlesex's 298.
Resuming in the morning on 143, with England spin bowler Ashley Giles at the other end on 30, Bell carried on where he had left off while his batting partner doubled his score to reach 62. Alan Richardson took four wickets for 87 with the ball.
In response, opener Andrew Strauss hit 37 before being caught by Jon Trott off the bowling of Alex Loudon. Middlesex finished the day on 137 for three in their second innings, just five runs ahead.
New Zealand captain Stephen Fleming scored a ton on his home debut for Nottinghamshire in their match with Sussex - as the home side built a massive first-innings total at Trent Bridge.
Fleming sped to 111, hitting 17 fours and a six as Notts continued their aggressive first innings on the third day following the loss of two early wickets.
Notts continued steadily, finishing for the day on 488 for six, a lead of 109.
Struggling Somerset trail Essex by 109 runs after closing on 128 for five in their second innings following an impressive hat-trick by Kiwi seamer Andre Adams.
The 29-year-old New Zealander had Mike Burns caught behind and then pinned Sanath Jayasuriya and James Hildreth lbw in his third over as the home side struggled to 128 for five in their second innings.
"The two lbws were both plum. But you are always surprised when the umpire gives a second decision the very next ball - it wouldn't happen with the umpires back in New Zealand," said Adams.