The Dutchman was set to face Djokovic at the grass-court exhibition event but the world number two pulled out, with an on-court announcement citing a wrist injury as the cause.
Haase was then handed the task of tackling Isner and responded by recording a 6-4 7-6 (7-3) triumph against the big-serving American.
Djokovic's decision not to take part will cast doubt over his fitness for Wimbledon, but Fabio Fognini is not likely to be able to take advantage even if the top seed is absent.
The Italian, whose talents are more suited to clay surfaces, has never got past the third round at the All England Club and was beaten 7-5 6-3 by Ernests Gulbis.
In the final match of the day, Jack Sock was taken the distance by Dominic Thiem before finally overcoming the Austrian in a tie-break, played instead of a full third set, 6-1 6-7 (4-7) 10-7.