Towering ruck-forward Ramsden (203cm) and first-round draft pick Josh Weddle will play their first games for the struggling Hawks at Marvel Stadium on Saturday.
Will Day (suspended) and Josh Ward (managed) return among five changes after last week's defeat to Adelaide.
But it is Lewis's inclusion that looms as being most impactful as last-placed Hawthorn seek attacking weapons that can help lift their league-worst average of 63 points a game.
The 24-year-old key forward, second in the Hawks' goal-kicking with 37 from 15 games last year, has not played at any level this season after sustaining a knee injury in January.
Hawthorn coach Sam Mitchell said Lewis has ticked every box with his rehabilitation.
"He looks match ready," Mitchell said.
"Does that mean he will be the best player on the ground and clunk everything? Absolutely not.
"We just need him to play his role and do his job."
Bulldogs superstar Smith returns after two weeks out with a calf injury as a direct replacement for fellow midfielder Tom Liberatore, who is out under concussion protocols.
Sydney have regained superstar Lance Franklin (knee) and key defender Tom McCartin (concussion) for Saturday's derby against GWS at the SCG.
The Giants have recalled Tom Green, Toby Bedford and Callum Brown with All-Australian defender Sam Taylor (hamstring), veteran Callan Ward (suspended) and Adam Kennedy (knee) all unavailable.
West Coast veteran Shannon Hurn is back from a week off to face Carlton, who have been bolstered by the inclusion of dashing defender Adam Saad (calf) and surprise early return of Sam Docherty (knee).
Former Brisbane and Bulldogs forward Josh Schache will play his first game for Melbourne, replacing injured teammate Harrison Petty against North Melbourne.
The Kangaroos have regained co-captain Jy Simpkin (hand) and recalled ruck-forward Callum Coleman-Jones.
Brisbane have picked Ryan Lester to play against Fremantle, who have brought back Sam Switkowski and Nathan O'Driscoll with Michael Frederick (adductor) out injured.
Ladder leaders St Kilda are unchanged for Friday night's clash with Port Adelaide, who welcome back key forward Charlie Dixon (knee).
Power trio Todd Marshall (concussion), Kane Farrell (jaw) and captain Tom Jonas (suspended) are all out.
Essendon have regained captain Zach Merrett after a one-match suspension for their meeting with Geelong on Sunday but Jayden Laverde (shoulder) will have a stint on the sidelines and Dyson Heppell has been managed.
Richmond have lost Marice Rioli Jnr (hamstring) and will rest Dion Prestia for the meeting with the gun midfielder's former club Gold Coast, who will be without co-captain Touk Miller (knee) and Levi Casboult (rested).
Key defender Nathan Murphy (concussion) and tough midfielder Taylor Adams (suspended) have been named in Collingwood's extended squad for the intriguing clash with Adelaide.
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