Everton teenager Barkley has started both Premier League games this season and scored a memorable goal on the opening day against Norwich, while Townsend has shone for Tottenham in the absence of wantaway Gareth Bale.
Southampton striker Rickie Lambert keeps his place after a match-winning debut against Scotland, while in-form Liverpool forward Daniel Sturridge returns after injury and Celtic's Fraser Forster gets the nod ahead of Stoke's Jack Butland as goalkeeping back-up.
England, two points behind Montenegro in Group H with a game in hand, will meet on Monday at St George's Park in preparation for the crunch double-header.
Hodgson's men host Moldova at Wembley on Friday, 6 September before travelling to Kiev to play Ukraine four days later.
Speaking at a press conference at Wembley on Tuesday afternoon, Hodgson said of Barkley: "He impressed me when I worked with him at St George's and at Sheffield Wednesday, and quite a few other people impressed at that that time - Raheem Sterling and of course Andros Townsend, who was on the radar before the U21s.
"In choosing these players we are giving ourselves a chance to look at players who are capable of having a bright future.
"Players like Barkley, Townsend and Sterling can make a difference and in a team they can be players that make a big impact. They are there on merit. It's nice that they're younger."
Goalkeepers: Fraser Forster (Celtic), Joe Hart (Manchester City), John Ruddy (Norwich City).
Defenders: Leighton Baines (Everton), Gary Cahill (Chelsea), Ashley Cole (Chelsea), Phil Jagielka (Everton), Glen Johnson (Liverpool), Phil Jones (Manchester United), Chris Smalling (Manchester United), Kyle Walker (Tottenham Hotspur).
Midfielders: Ross Barkley (Everton), Michael Carrick (Manchester United), Tom Cleverley (Manchester United), Steven Gerrard (Liverpool), Frank Lampard (Chelsea), James Milner (Manchester City), Raheem Sterling (Liverpool), Andros Townsend (Tottenham Hotspur), Theo Walcott (Arsenal), Jack Wilshere (Arsenal).
Forwards: Jermain Defoe (Tottenham Hotspur), Rickie Lambert (Southampton), Wayne Rooney (Manchester United), Daniel Sturridge (Liverpool), Danny Welbeck (Manchester United), Ashley Young (Manchester United).