This river, from the headwater, reaches large estuary, ultimately (6)
I believe the answer is:
mersey
'this river' is the definition.
(English river)
'from the headwater reaches large estuary ultimately' is the wordplay.
'ultimately' indicates one should take the final letters.
The last letters of 'from the headwater reaches large estuary' are 'MERSEY'.
(Other definitions for mersey that I've seen before include "Scouse river" , "River with ferry and tunnel" , "River rising in Derbyshire and flowing into the Irish Sea" , "River linking Greater Manchester and Liverpool" , "Liverpool's river" .)