Tomic extended his winning run to six matches with a 6-3 6-2 thrashing of Colombian Alejandro Gonzalez on the hard courts in Washington.
The Aussie youngster, winner of last week's Claro Open Colombia to climb back into the top 100, needed just 58 minutes to advance at the ATP 500 event.
He served 10 aces and broke serve three times to set up a meeting with Uzbek 15th seed Denis Istomin.
Matosevic set up a meeting with Hewitt after a 6-4 7-5 victory against Ukraine's Illya Marchenko.
Slovakia's Lukas Lacko built on his quarter-final appearance in Atlanta last week by reaching the second round thanks to a 7-5 6-3 win over Canadian wildcard Filip Peliwo.
Awaiting Lacko in the second round is 16th seed Lu Yen-hsun of Chinese Taipei.
Frenchman Benoit Paire was on court for just 39 minutes, disposing of Canadian Frank Dancevic 6-4 6-0.
In a battle between two American qualifiers, Rajeev Ram edged teenager Jared Donaldson 6-7 (1-7) 6-4 7-5.
Donaldson, 17, lost his cool late in the loss to veteran Ram.
Qualifier Robby Ginepri was untroubled in a 6-4 6-2 win over Colombian Alejandro Falla and American Tim Smyczek crushed countryman and qualifier Alex Kuznetsov 6-3 6-0.
Russia's Evgeny Donskoy beat 16-year-old American Francis Tiafoe 6-4 6-4 and Tunisian Malek Jaziri upset Ukraine's Sergiy Stakhovsky 7-6 (7-2) 6-4.
American Donald Young battled to a 6-4 4-6 6-4 win over Japanese qualifier Yuichi Sugita.