She was one of just 10 women in tennis history to have won singles titles at all four Grand Slams.
The Serbian world No. 1 increased his Grand Slam tally to 19 titles, and is now one adrift of the men's record held by Roger Federer and Rafael Nadal.
Krejcikova became the first player to win both the women's singles and doubles title in Paris since Frenchwoman Mary Pierce completed the feat in 2000.
The 25-year-old is the first Czech to lift the Suzanne Lenglen Cup since Hana Mandlikova, who represented Czechoslovakia, triumphed in 1981.
Djokovic came from a set down in a spellbinding semifinal to inflict only a third ever defeat on the Parisian clay for Nadal.
Krejcikova became the first Czech woman in 40 years to reach the French Open final as she beat Greek 17th seed Maria Sakkari 7-5, 4-6, 9-7 in a nail-biting, see-saw contest.
Djokovic repelled a stirring fightback by Italian Matteo Berrettini to claim a 6-3, 6-2, 6-7(5), 7-5 victory.
Sakkari dictated most of the points and was greatly helped by her opponent's unforced errors.
The Czech beat a nervy Coco Gauff 7-6(6), 6-3.
The Greek got revenge for his Australian Open semifinal loss to the Russian this year and improved his Grand Slam quarterfinal record to 4-0 with a 6-3, 7-6(3), 7-5 win that teed up a last-four clash against Germany's Alexander Zverev.