Mannarino, who had beaten Albot in their only previous encounter in Sofia last year, could not repeat that feat again as the Moldovan was clearly at his best.
Isner, 35, owns 15 ATP titles, including 13 on US soil, but has never lifted the trophy at Delray Beach.
US Open 2020: Borna Coric stages epic comeback to stun Stefanos Tsitsipas; Novak Djokovic sails into last 16
Croatia's 27th seed Borna Coric staged a remarkable Houdini act to stun fourth seed Stefanos Tsitsipas in a 4hr 36min late-night thriller.
After Benoit Paire, a Frenchman seeded 17th, was taken out of the draw Sunday because of his test result, contact tracing determined there were seven players who potentially could have been exposed to COVID-19.
US Open 2020: Talk of 'fake bubble,' 'bubble in bubble' on Day 1 as Novak Djokovic, Naomi Osaka post wins
US Open tournament director Stacey Allaster said players potentially exposed to the virus because of contact with Paire now must be tested daily for COVID-19, instead of every four days.
US Open 2020: Players believed to have come in contact with Benoit Paire to remain in event, say organisers
Several players including Richard Gasquet, Adrian Mannarino and Edouard Roger-Vasselin had been in contact with Paire, according to French sports publication L'Equipe.
Australian Open 2020: Rafael Nadal begins tournament with easy win; 'Next Gen' star Jannik Sinner makes successful debut
The 33-year-old Nadal dropped a service game once in each of the first two sets but was too dominant for No. 73-ranked Dellien
ATP Paris Masters 2019: Daniil Medvedev suffers first defeat since US Open final; defending champion Karen Khachanov bundled out
Medvedev, who had reached six successive finals, looked in control when he took the first set but he ultimately paid for failing to convert 14 of the 15 break points he carved out
Japan Open 2019: Novak Djokovic beats third-seeded David Goffin in semi-final, to face John Millman in final
After controlling the first set, Djokovic broke Goffin in the first game of the second with a perfectly-placed volley at the net
Zhuhai Championships: Australia's Alex de Minaur clinches season's third title with win over Adrian Mannarino in final
De Minaur, currently 31 in the world, overcame the Frenchman in a little over two hours to cap an impressive week for the 20-year-old.
Zhuhai Championships 2019: Andy Murray feels he is playing 'top-70' level tennis after early exit from competition
Murray said he was pleased with aspects of his performance against 20-year-old De Minaur and his hip was fine, but admitted that he still lacked match fitness.
Zhuhai Championships 2019: Stefanos Tsitsipas says he doesn't want to wait for 'Big three' to retire, wants to beat them now
Tsitsipas, who hails from Greece, said that he doesn't want to wait around for an opportunity but create it now and beat the 'Big 3' to advance in the rankings
Rogers Cup: Rafael Nadal overtakes Roger Federer to become player with most Masters win; Dominic Thiem advances to last-eight
Rafael Nadal stepped closer to a record 35th Masters 1000 title, dispatching Guido Pella to power into the Montreal Masters quarter-finals.
Spanish tennis player Feliciano Lopez categorically denied a report that a match he and doubles partner Marc Lopez lost at Wimbledon in 2017 was fixed.
The tournament top seed Rafael Nadal seized the advantage in the opening set, scoring a break to go 3-1 ahead with a delicate lob that left Zverev floundering
Delray Beach Open: Second seed John Isner books quarter-final berth with confident win over Lukas Lacko
Second-seeded John Isner booked a quarter-final berth at the ATP Delray Beach Open on Wednesday with a confident 6-4, 6-3 victory over Slovakia's Lukas Lacko.
Delray Beach Open: Juan Martin del Potro bounces back from injury to beat Yoshihito Nishioka; Frances Tiafoe crashes out
Del Potro, who won the tournament in Florida in 2011, will next face big-serving American Reilly Opelka after last week’s New York Open champion saw off countryman Tennys Sandgren 6-4, 6-0 earlier in the day.
Kremlin Cup: Teary Daria Kasatkina beats Tunisian qualifier Ons Jabeur in tough three-setter to clinch title
After clinching the match, Kasatkina fell to the court and wept for joy. Then she walked around the net as Jabeur struggled to her feet and the two hugged each other.
Cincinnati Masters: Novak Djokovic overcomes stomach issues to beat Adrian Mannarino; Garbine Muguruza ousted
Novak Djokovic battled stomach issues to beat Adrian Mannarino and reach the third round in Cincinnati on Wednesday as women's title holder Garbine Muguruza crashed out.