+----------------------------- In the scalar $s (interpreted as a str
+ing),
 |       +--------------------- if you find an _ (underscore)
 |       |   +----------------- that's followed by 0 or more of anythi
+ng but an _ (underscore) 
 |       |   |                  and then the end-of-string,    
 |       |   |             + -- replace it with a , (comma).
 |       |   |             |
 V       V   V             V
$s =~ s{ _ (?= [^_]* \z) }{,}xms;
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Update: See "Look-Around Assertions" in the Extended Patterns of perlre.

(And the use of  <code> ... </code> tags would still be much appreciated.)

Another Update: If you have Perl version 5.10+, another way (see  \K in Extended Patterns):

c:\@Work\Perl\monks>perl -wMstrict -le
"use 5.010;
 ;;
 my @flist = qw(
   1st-device-CA_Eth.0/1
   2nd-device_TX_Gig.1/1
   3rd_device_MO_Gig.1/1
   );
 ;;
 for my $s (@flist) {
   print qq{'$s'};
   $s =~ s{ .* \K  _ }{,}xms;
   print qq{'$s'};
   print '';
   }
"
'1st-device-CA_Eth.0/1'
'1st-device-CA,Eth.0/1'

'2nd-device_TX_Gig.1/1'
'2nd-device_TX,Gig.1/1'

'3rd_device_MO_Gig.1/1'
'3rd_device_MO,Gig.1/1'
[download]