Isner powered his way past Italian Fabio Fognini 6-3 6-2, while the bearded Johnson, fresh off his Rio Olympics bronze in the doubles, defeated Argentine left-hander Federico Delbonis 6-4 7-5 to reach the second round of the Masters 1000 event.
US teenager Jared Donaldson is threatening to join them after winning the first set 6-2 against world No 4 Stanislas Wawrinka.
The 18-year-old wildcard twice broke the second seed in winning the opening set, helped by a rash of unforced errors from Wawrinka, before the Swiss settled down and swept the first three games of the second set.
