While studies on residential and job mobility are typically conducted on a micro scale, an examination of region-wide mobility dynamics can also be meaningful, as it can reflect the importance of system-wide factors and complex interlinkages among numerous micro-level decisions. This study explores how region-wide residential and job mobility rates vary in the US and identifies factors that shape their variation with emphasis on the interplay between the two mobility variables for the periods before (2005–2007) and during (2008–2010) the recent recession. An analysis of the data for 342 US metropolitan areas shows that job mobility had a sizable positive impact on residential mobility during both time spans, while the reverse connection was found to be relatively weaker and context-sensitive. The analysis also detects the critical roles of housing market conditions and regional economic structures, suggesting that mobility decisions are largely shaped by various macro-level factors.