The β1-adrenergic receptor (β1-AR) being considered among the potential G-protein coupled receptors (GPCRs) is primarily abundant in the prominent component (i.e., heart) of the cardiovascular system, exhibiting a huge significance in the modulation of cardiac function. Endocytosis and signaling of β1-AR are essential processes concerning adrenergic signaling and cardiac physiology; however, its activity is controlled by catecholamines, including norepinephrine and epinephrine, released by the sympathetic nervous system. β1-AR kicks off the G proteins (e.g., Gs protein) inception upon activation by a ligand that in turn triggers adenylyl cyclase (AC). Augmented levels of AC can lead to the accumulation of cyclic adenosine monophosphate (cAMP) levels, thereby directing a series of downstream signaling events including the activation of protein kinase A (PKA). β1-ARs undergo β-arrestin-mediated endocytosis for desensitization and downregulation processes to prevent their prolonged activation. The impact of β1-AR endocytosis on the pharmacological responses to β-blockers and other drugs targeting β1-ARs is to be explored extensively. Also, understanding the interaction and influence of β1-ARs on the trafficking and signaling of GPCRs concerning cardiac function and disease requires in-depth knowledge. This chapter demonstrates the cognizance of the primary structural arrangement including the functions of β1-ARs and their mechanism of action concerning endocytosis and GPCR-based downstream signaling targets and their role in myocardial infarction.