The unseeded Krejcikova dominated the opening set but had to fend off a Pavlyuchenkova fightback to win 6-1 2-6 6-4 at Roland Garros on Sunday (AEST).
Making only her fifth appearance in a main singles draw at a Major compared to her Russian opponent's 52nd, Krejcikova added a first grand slam singles title to her five doubles triumphs.
Krejcikova broke twice in a tense final set in the battle between two first-time Major singles finalists on Court Philippe-Chatrier, becoming the first Czech woman to win the title in Paris since Hana Mandlikova in 1981.
Pavlyuchenkova won the opening point with a measured forehand winner, with Krejcikova looking understandably nervy as she was broken in the first game but she soon warmed to the task.
The 25-year-old took command on a humid afternoon, dictating rally after rally in composed fashion with precise groundstrokes off both wings and deft drop shots.
Krejcikova returned superbly and had a 5-1 lead when a Pavlyuchenkova forehand looped out before coming from 0-30 down to wrap up a one-sided opening set in only 31 minutes.
Pavlyuchenkova, four years older than her opponent, finally held after fending off a break point in the first game of the second set and went 2-0 up with a rasping backhand winner down the line after a sublime drop-shot.
A thunderous, deep Pavlyuchenkova return enabled her to move a game away from levelling the match but she had to take a medical timeout when leading 5-2 after a Krejcikova break.
The No.31 seed returned to the court with strapping on her left thigh and broke again to take the second set, but a double fault gifted Krejcikova an early break in the decider.
Pavlyuchenkova hit straight back, letting out a roar after a brilliant cross-court forehand to make it 2-2, only for Krejcikova to secure a break to love for a 4-3 lead with a forehand winner.
The battling Pavlyuchenkova did not appear to be moving as freely but saved two match points to stay alive before Krejcikova served out the match, raising her arms aloft after her opponent sent a forehand long.