We previously identified an 1-AR-ERK (1A-adrenergic receptor–extracellular signal-regulated kinase) survival signaling pathway in adult cardiac myocytes. Here, we investigated localization of 1-AR subtypes (1A and 1B) and how their localization influences 1-AR signaling in cardiac myocytes. Using binding assays on myocyte subcellular fractions or a fluorescent 1-AR antagonist, we localized endogenous 1-ARs to the nucleus in wild-type adult cardiac myocytes. To clarify 1 subtype localization, we reconstituted 1 signaling in cultured 1A- and 1B-AR double knockout cardiac myocytes using 1-AR–green fluorescent protein (GFP) fusion proteins. Similar to endogenous 1-ARs and 1A- and 1B-GFP colocalized with LAP2 at the nuclear membrane. 1-AR nuclear localization was confirmed in vivo using 1-AR-GFP transgenic mice. The 1-signaling partners Gq and phospholipase C1 also colocalized with 1-ARs only at the nuclear membrane. Furthermore, we observed rapid catecholamine uptake mediated by norepinephrine-uptake-2 and found that 1-mediated activation of ERK was not inhibited by a membrane impermeant 1-blocker, suggesting 1 signaling is initiated at the nucleus. Contrary to prior studies, we did not observe 1-AR localization to caveolae, but we found that 1-AR signaling initiated at the nucleus led to activated ERK localized to caveolae. In summary, our results show that nuclear 1-ARs transduce signals to caveolae at the plasma membrane in cardiac myocytes.